Estrogen's Role Focus of Work on Brain

Songbirds — which make up about half the world’s 9,000 bird species — have an astonishing characteristic.

During the spring, parts of their brains nearly double in size, shrinking later to normal size.

That neuroplasticity, and the role of estrogen in songbirds’ ability to both change the size of and repair injuries to their brains, is what drew College of Arts and Sciences biology professor Colin Saldanha to them.

For when songbirds’ brains are injured, they use estrogen to slow degeneration. Which is why Saldanha’s research could have important implications in treating Alzheimer’s, stroke, and Parkinson’s disease.

Synaptocrine Signaling

Once erroneously considered an exclusively female hormone, in a vast number of species estrogen is present in the brains of males and females. Indeed, some parts of the male brain have higher levels of estrogen than female brains, Saldanha notes.

But if estrogen is simply dumped into the blood stream where every tissue has access to it, how is the amount and timing of its production controlled?

“In the last 10 years we have discovered the enzyme that makes estrogen is localized to very specific portions of nerve cells, and our big surprise, which we published in 2005, was that individual synapses — and these are the connections between neurons, these are the points at which neurons transfer information from one to another — individual synapses are capable of synthesizing estrogen,” Saldanha explains.

“So now we’re talking about a very specific hormonal control of information processing. We’re miles away from the dump the hormone into the blood idea. Now we’re talking about an individual neuron being able to create the high level of estradial in the precise neuron that it is talking to downstream. It is a highly specific form of neuro and hormonal communication. In fact we had to come up with a name for this because there wasn’t a name for it in the literature. We have called it synaptocrine signaling.”

Importantly, a specific target can be fed high levels of the hormone while excluding it from neighboring cells, Saldanha says. “So you see how it’s dramatically different from dumping it into the vasculature where it just goes everywhere and you have no control over who gets it and when it gets it. This way it’s a very specific targeting.”

Hormone Synthesis

Two major types of cells make up the brain: neurons and glia. Glia, from the Middle Greek word for glue, were long considered nothing more than the stuff that held together the truly important cells, the neurons.

That turned out to be wrong.

The glial cells carry out important tasks, such as supplying nutrients, acting as toxic dumps, and helping with neurotransmission. Saldanha and his fellow researchers discovered that these cells, under the right conditions, can also synthesize estrogen.

“We discovered if you injure the brain of a songbird, these glial cells — which normally never express this enzyme that makes estradial — switch to the ability to make estrogen within 24 hours.”

Why is that important?

It slows down brain degeneration. And that could have important implications for the treatment of diseases like Alzheimer’s, Parkinson’s, and stroke.

Estrogen and Learning

Scientists believe that the synapses where information is transferred from neuron to neuron is where learning occurs. And most biologists think the process of learning strengthens synaptic connections, Saldanha says.

The breakdown of these connections may be the physical reflection of how we forget something.

Saldanha and his fellow researchers think the ability to synthesize estrogen in synaptic boutons — an area within a part of the neuron called an axon that contains neurotransmitters — and in astroglia — a type of non-neuronal brain cell — may have a role in strengthening learning, as well as memory and neural degeneration, protection, and repair.

They’re testing the hypothesis that this ability to make estrogen may be how synapses are strengthened and information processing made more efficient.

“When that strengthening breaks down, reflected by maybe a decrease in estrogen synthetic ability, perhaps that is one way in which information processing decreases and learning decreases or forgetting increases,” he says.

Songbirds have something to teach us in this regard because they never have strokes; their glial cells quickly switch on the ability to make estrogen.

Since 2002, the National Institutes of Health has awarded Saldanha about $3.1 million in grants to further his research, which he says boils down to three phases: Does the mechanism exist? How is it regulated? What does it do?

Now that the first two questions have been answered, the last question will be the focus of the next cycle of research.

A Song of His Own

Back in the days when he was a postdoc at the University of California–Los Angeles, before he was a full-time faculty member, Saldanha had time to pursue one of his great passions: singing.

Back then, he was chair of the board and first tenor for the Gay Men’s Chorus of Los Angeles. The chorus had three major concerts a year, put out CDs, and went on a European tour.

Perhaps his most moving experience with the chorus was its reception in 1999 at Tchaikovsky Hall in St. Petersburg. “They stood when we sang ‘We Shall Overcome,’” he recalls. “I’m getting goose bumps just telling this story. It was like singing a national anthem. We started singing and everyone got to their feet and then of course we couldn’t sing anymore because we were just blubbering. It was hard to keep going.”

Saldanha and his wife have long supported the gay men’s chorus and GALA — an organization of GLBT and GLBT-allied choruses — for reasons beyond the music.

“My involvement with GALA and the gay chorus movement is basically because it’s the next public civil rights issue,” he says.

“Ten years ago when we were in LA trying to start this, we did it through music. The whole point was, we’d start every board meeting with the simple idea that we wanted to make sure that every city would be able to say our gay chorus is better than yours. And that was the point because you wanted to become part of the rubric of the fine arts.”

Spicing Up His Life

Describing his work, Saldanha makes the rigors of science — the quest for new knowledge, the years of careful testing, retesting, and testing again of results — sound fascinating, even fun. So it’s no surprise that the self-described Food Network addict describes his enjoyment of cooking this way.

“It’s a lot like science. It’s tinkering around, and when it comes down to it there’s a lot of chemistry in there. You start appreciating why it is good to mix sausage and seafood . . . You realize how salt and sugar go together way better than just sugar and cream, so throwing a handful of salt into a dessert just makes it fantastic.”

Saldanha will discuss his work on Wednesday, February 15, 2012, as part of the CAS Celebration of Research. The presentation will be from noon to 1:30 p.m. in Mary Graydon Center Room 5.